This month’s Continuing Education topic is pharmacogenomics. That is the unifying theme of three informative articles: “Genomics: gearing up for the laboratory of the future” by Harry Glorikian, BA, MBA; Companion diagnostics: an emerging component in personalized medicine” by Bruce Patterson, MD; and “Pharmacogenetics and pain management” by Maria Chianta, PharmD, and Maria Guevara, PharmD.
You may notice an interesting thing about the three pharamacogenomics articles (pp. 8-11): none of them has the word pharmacogenomics in its title.
This is due, in part, to the fact that when a topic is relatively new, often its terminology is unsettled. Different practitioners use different terms, and that is reflected in writing about the topic. The words pharmacogenomics and pharmacogenetics are often used interchangeably. Is that correct? Many experts say no, not exactly; there is a difference.
PharmGKB, an internationally recognized scientific and clinical knowledge resource, has this definition on its website (http://www.pharmgkb.org/page/faqs):
What is the difference between pharmacogenetics and pharmacogenomics? In general, pharmacogenetics usually refers to how variation in one single gene influences the response to a single drug. Pharmacogenomics is a broader term, which studies how all of the genes (the genome) can influence responses to drugs.
The distinction seems to be one that is worth preserving.
On a related note: Pharmacogenomics is an exciting field with far-reaching implications for healthcare. But science is a process of two-steps-forward, one-step-back. The most well known application of pharmacogenomics is warfarin dosing, based on VKCOR and CYP2C9. Testing for this has received FDA approval and exists in various market kits. In an article electronically published in the North Carolina Journal of Medicine on November 19, 2013, Daniel E. Jones, MD, and Roberta Wines, MD, collected and analyzed clinical data and came to the conclusion that, in this case at least, pharmacogenomic testing showed little to no clinical benefit. The findings, reflected in their article “Pharmacogenomic Testing and the Prospect of Individualized Treatment,” reminded the genomics community that the technique is in its infancy. (Generally similar conclusions were reached by a second unrelated study published in the same journal.)
“Randomized controlled trials have not yet shown that genotype-guided Warfarin dosing improves clinical outcome,” Drs. Jones and Wines write. “No rigorous studies have established a connection between use of a genotype-guided strategy and improved outcomes, and the ACCF/AHA guidelines explain that the clinical utility of genotypic testing has not been established.” They conclude, “Good evidence of clinical utility must be obtained before pharmacogenomic testing is widely implemented.”
However, they report, such evidence may be forthcoming. As more studies are completed and more data become available, perspectives on the ability of genotype testing to predict dosing regimens may change. “The Clarification of Optimal Anticoagulation through Genetics (COAG) trial—a large, multicenter, double-blind, randomized trial that is currently ongoing—should help to clarify the clinical utility of genotype-guided dosing.” Help is on the way!
Certainly, not all studies yield immediately encouraging results—and, for scientists, that is fine. Researchers seek meaningful, repeatable results. When they do not get the “right” ones from a particular study, they are still getting information that will help them eventually find the path toward clinically actionable data. They are learning what they will need to learn from further research. So will it be with pharmacogenomics. The technique is still very new, and it will need to demonstrate clinical utility on a case-by-case basis. There may be setbacks along the way—but if they increase knowledge, are they really setbacks?
